Chemical and Pharmaceutical Bulletin p. 2042 - 2048 (1994)
Update date:2022-09-26
Topics:
Ohno
Koumori
Adachi
Mizukoshi
Nagasaka
Ichihara
A series of new (5R,8S,10R)-ergoline derivatives was synthesized, and their antihypertensive and dopaminergic activities were evaluated in conscious spontaneously hypertensive rats and in rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra, respectively. (5R,8S,10R)-6-Methyl-8-ergolinemethanols, prepared from the corresponding ergolinecarboxylates, were converted to the tosylates, which were treated with various five-membered heterocycles containing nitrogen atoms to afford the new ergolines. (5R,8S,10R)-8-(1-Imidazolylmethyl)-6-methylergoline (5a, BAM-2101) and (5R,8S,10R)-2-bromo-6-methyl-8-(1,2,4-triazol-1-ylmethyl)ergoline (7c, BAM-2202) exhibited potent antihypertensive activities. The maximum falls of systolic blood presure after oral administration of 5a and 7c at 3 mg/kg were 95 and 132 mmHg, respectively, while those of cianergoline, bromocriptine mesylate, hydralazine, and nifedipine at the same dose were 40, 37, 47, and 49 mmHg, respectively. The durations of significant antihypertensive effects of these compounds except nifedipine were more than 7 h. None of the ergolines exhibited potent dopaminergic activity. Structure-activity relationships are discussed.
View Morezhuzhou zhongle chemical co. ltd.
Contact:+86-0731 28228409
Address:Zhuzhou, Hunan, China
website:http://www.simagchem.com
Contact:+86-592-2680277
Address:21/F Hualong Office Building,No.6 Hubin East Road, Xiamen,China
YingYing Pharmaceutical Co.,Ltd
Contact:86-18854126208
Address:55#, yingxiongshan road
Guangzhou PI & PI Biotech Inc. Ltd.
Contact:+86-20-81716320
Address:Suite 501,198 Kaiyuan Ave.,Science City, Guangzhou,China
Melone Pharmaceutical Co., ltd
Contact:+86-411 82593920, 82593631
Address:No 232, JInma Roda, Development Zone, Dalian, China
Doi:10.1016/S0040-4039(00)98584-8
(1985)Doi:10.1002/ejic.201900110
(2019)Doi:10.1016/S0040-4039(00)98115-2
(1985)Doi:10.1021/jo991328h
(2000)Doi:10.1002/jccs.200500086
(2005)Doi:10.1002/ejic.201500489
(2015)